Synthesis and Antiparasitic Activity of New Trithiolato-Bridged Dinuclear Ruthenium(II)-arene-carbohydrate Conjugates.

Holzer, Isabelle; Desiatkina, Oksana; Anghel, Nicoleta; Johns, Serena K; Boubaker, Ghalia; Hemphill, Andrew; Furrer, Julien; Păunescu, Emilia (2023). Synthesis and Antiparasitic Activity of New Trithiolato-Bridged Dinuclear Ruthenium(II)-arene-carbohydrate Conjugates. Molecules, 28(2) MDPI 10.3390/molecules28020902

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Eight novel carbohydrate-tethered trithiolato dinuclear ruthenium(II)-arene complexes were synthesized using CuAAC 'click' (Cu(I)-catalyzed azide-alkyne cycloaddition) reactions, and there in vitro activity against transgenic T. gondii tachyzoites constitutively expressing β-galactosidase (T. gondii β-gal) and in non-infected human foreskin fibroblasts, HFF, was determined at 0.1 and 1 µM. When evaluated at 1 µM, seven diruthenium-carbohydrate conjugates strongly impaired parasite proliferation by >90%, while HFF viability was retained at 50% or more, and they were further subjected to the half-maximal inhibitory concentration (IC50) measurement on T. gondii β-gal. Results revealed that the biological activity of the hybrids was influenced both by the nature of the carbohydrate (glucose vs. galactose) appended on ruthenium complex and the type/length of the linker between the two units. 23 and 26, two galactose-based diruthenium conjugates, exhibited low IC50 values and reduced effect on HFF viability when applied at 2.5 µM (23: IC50 = 0.032 µM/HFF viability 92% and 26: IC50 = 0.153 µM/HFF viability 97%). Remarkably, compounds 23 and 26 performed significantly better than the corresponding carbohydrate non-modified diruthenium complexes, showing that this type of conjugates are a promising approach for obtaining new antiparasitic compounds with reduced toxicity.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Holzer, Isabelle, Desiatkina, Oksana, Anghel, Nicoleta, Johns, Serena Kudzai, Boubaker, Ghalia, Hemphill, Andrew, Furrer, Julien, Paunescu, Emilia

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry
600 Technology > 630 Agriculture
000 Computer science, knowledge & systems

ISSN:

1420-3049

Publisher:

MDPI

Language:

English

Submitter:

Pubmed Import

Date Deposited:

26 Jan 2023 13:16

Last Modified:

07 Aug 2024 15:45

Publisher DOI:

10.3390/molecules28020902

PubMed ID:

36677958

Uncontrolled Keywords:

CuAAC reactions Toxoplasma gondii antiparasitic auxotrophy bioorganometallic carbohydrates human foreskin fibroblasts ruthenium(II)-arene complexes toxicity

BORIS DOI:

10.48350/177754

URI:

https://boris.unibe.ch/id/eprint/177754

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